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Introduction to Special Issue on Bladder Control in Neurological Diseases
Experimental Neurology 285 (2016) 109
Contents lists available at ScienceDirect
Experimental Neurology journal homepage: www.elsevier.com/locate/yexnr
Editorial
Introduction to Special Issue on Bladder Control in Neurological Diseases Neurological diseases represent a common cause of impaired lower urinary tract function. These conditions include neurodegenerative and neuro-inflammatory disorders, brain and spinal cord trauma, stroke, as well as a variety of pathologies and injuries affecting the peripheral nervous system. Lower urinary tract dysfunction in the setting of neurological disease and injury may present clinically as an overactive or underactive bladder syndrome and result in long-term disabilities. For many patients with bladder dysfunction, treatment options are limited. Research progress to better understand the effects of neurological diseases on bladder control and the development of new treatment strategies to overcome bladder dysfunction are urgently needed for this large and underserved patient population. This special issue is focused on topics addressing current and emerging new knowledge on bladder control and dysfunction in neurological conditions and relevant experimental models. The special issue brings together original research and review articles by experts on basic, translational, and clinical studies of bladder function in a broad range of neurological conditions. The issue is divided into different themes. The importance of neurotrophic factors for the development or maintenance of micturition reflexes is highlighted by the use experimental models that either overexpress or show reduced levels of specific neurotrophic factors. Girard et al. show that the postnatal development of the vesicovesical reflex is accelerated in mice with overexpression of nerve growth factor with an associated increase in peptidergic innervation of the suburothelial nerve plexus. Bladder afferents may also be regulated by other neurotrophic factors. Xia et al. report that a colon-to-bladder cross sensitization taking place from an induced colitis in rats is regulated by signal transduction that involves the upregulation of brain-derived neurotrophic factor in dorsal root ganglia. Modulation of lower urinary tract function may be achieved using pharmacological approaches in a variety of neurological conditions. For this purpose, it is important to consider both neurotransmitter and receptor functions within the central nervous system and peripheral end organs. Hou et al. show that dopamine is present in the rat spinal cord and that modulation of dopaminergic activity can influence bladder function and voiding efficiency. Ungerer et al. report that cholinergic activation of urothelial or suburothelial receptors can modulate micturition reflexes and the functional properties of bladder contractions in cats with a chronic spinal cord injury. The use of botulinum toxin A has been translated into clinical practice and is used for the treatment of refractory detrusor overactivity. A spinal cord injury may result in neurogenic detrusor overactivity with a combination of high frequency bladder contractions and increased intravesical pressure resulting in an increased risk for urinary incontinence. Injections of botulinum toxin A has emerged as an effective approach to inhibit voiding contractions but may contribute to urinary retention, in part likely due to parasympathetic efferent inhibition. In an attempt to overcome this potential treatment limitation, Coelho et
http://dx.doi.org/10.1016/j.expneurol.2016.10.004 0014-4886/© 2016 Published by Elsevier Inc.
al. describe intrathecal administration of botulinum toxin A as a new and alternative approach to more selectively inhibit sensory fibers while preserving voiding contractions in a rat model. Most studies on the effects of intradetrusor injections of botulinum toxin A have focused on micturition reflexes and voiding function. The potential for this localized therapy to exert acute or long-term systemic effects has been less comprehensively addressed, especially as subjects may undergo repeat bladder wall injections. Mehnert et al. examine the effects of onabotulinumtoxinA on cardiac function in patients with neurogenic detrusor overactivity and age-matched control subjects. Neuromodulation may alter nerve activity by delivery of, for instance, electrical stimulation to targeted sites. Several innovative approaches, including pudendal nerve stimulation, are emerging for augmenting lower urinary tract function. Langdale and Grill report that improved voiding efficiency can be achieved in both rats and cats following phasic activation of the external urethral sphincter. Gad et al. show that acute epidural stimulation over the rat spinal cord can modulate lower urinary tract function and that sensorimotor networks controlling bladder function and locomotor function are highly integrated. The final paper addresses underactive bladder syndromes as an emerging and rapidly growing area of research. It has in recent times been more recognized that an underactive bladder may develop as a direct result of neurological injury and disease but also as a late development from an initially overactive bladder. However, mechanisms underlying the pathobiology of an underactive bladder are incompletely understood, and new experimental models are needed to address the needs for this underserved patient population. Chang and Havton reviews recently developed experimental models for neurogenic underactive bladder studies. Research on bladder control in the setting of neurological diseases has shown significant growth in recent years, and this progress is also reflected in the several contributions to this special issue. However, many challenges remains for this research field and will require collaborative and multi-disciplinary approaches to overcome. Some of these challenges include the identification of the most promising basic science discoveries for clinical translation and the development and validation of pre-clinical models that are the most relevant for human neurological conditions. It is my hope that the research articles in this special issue will increase awareness in the research community about the importance of research on lower urinary tract dysfunction and stimulate both established and young investigators to continue the development of improved experimental models and approaches for the study of bladder function in the setting of neurological conditions. Leif A. Havton Departments of Neurology and Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 E-mail address: [email protected]
Contents lists available at ScienceDirect
Experimental Neurology journal homepage: www.elsevier.com/locate/yexnr
Editorial
Introduction to Special Issue on Bladder Control in Neurological Diseases Neurological diseases represent a common cause of impaired lower urinary tract function. These conditions include neurodegenerative and neuro-inflammatory disorders, brain and spinal cord trauma, stroke, as well as a variety of pathologies and injuries affecting the peripheral nervous system. Lower urinary tract dysfunction in the setting of neurological disease and injury may present clinically as an overactive or underactive bladder syndrome and result in long-term disabilities. For many patients with bladder dysfunction, treatment options are limited. Research progress to better understand the effects of neurological diseases on bladder control and the development of new treatment strategies to overcome bladder dysfunction are urgently needed for this large and underserved patient population. This special issue is focused on topics addressing current and emerging new knowledge on bladder control and dysfunction in neurological conditions and relevant experimental models. The special issue brings together original research and review articles by experts on basic, translational, and clinical studies of bladder function in a broad range of neurological conditions. The issue is divided into different themes. The importance of neurotrophic factors for the development or maintenance of micturition reflexes is highlighted by the use experimental models that either overexpress or show reduced levels of specific neurotrophic factors. Girard et al. show that the postnatal development of the vesicovesical reflex is accelerated in mice with overexpression of nerve growth factor with an associated increase in peptidergic innervation of the suburothelial nerve plexus. Bladder afferents may also be regulated by other neurotrophic factors. Xia et al. report that a colon-to-bladder cross sensitization taking place from an induced colitis in rats is regulated by signal transduction that involves the upregulation of brain-derived neurotrophic factor in dorsal root ganglia. Modulation of lower urinary tract function may be achieved using pharmacological approaches in a variety of neurological conditions. For this purpose, it is important to consider both neurotransmitter and receptor functions within the central nervous system and peripheral end organs. Hou et al. show that dopamine is present in the rat spinal cord and that modulation of dopaminergic activity can influence bladder function and voiding efficiency. Ungerer et al. report that cholinergic activation of urothelial or suburothelial receptors can modulate micturition reflexes and the functional properties of bladder contractions in cats with a chronic spinal cord injury. The use of botulinum toxin A has been translated into clinical practice and is used for the treatment of refractory detrusor overactivity. A spinal cord injury may result in neurogenic detrusor overactivity with a combination of high frequency bladder contractions and increased intravesical pressure resulting in an increased risk for urinary incontinence. Injections of botulinum toxin A has emerged as an effective approach to inhibit voiding contractions but may contribute to urinary retention, in part likely due to parasympathetic efferent inhibition. In an attempt to overcome this potential treatment limitation, Coelho et
http://dx.doi.org/10.1016/j.expneurol.2016.10.004 0014-4886/© 2016 Published by Elsevier Inc.
al. describe intrathecal administration of botulinum toxin A as a new and alternative approach to more selectively inhibit sensory fibers while preserving voiding contractions in a rat model. Most studies on the effects of intradetrusor injections of botulinum toxin A have focused on micturition reflexes and voiding function. The potential for this localized therapy to exert acute or long-term systemic effects has been less comprehensively addressed, especially as subjects may undergo repeat bladder wall injections. Mehnert et al. examine the effects of onabotulinumtoxinA on cardiac function in patients with neurogenic detrusor overactivity and age-matched control subjects. Neuromodulation may alter nerve activity by delivery of, for instance, electrical stimulation to targeted sites. Several innovative approaches, including pudendal nerve stimulation, are emerging for augmenting lower urinary tract function. Langdale and Grill report that improved voiding efficiency can be achieved in both rats and cats following phasic activation of the external urethral sphincter. Gad et al. show that acute epidural stimulation over the rat spinal cord can modulate lower urinary tract function and that sensorimotor networks controlling bladder function and locomotor function are highly integrated. The final paper addresses underactive bladder syndromes as an emerging and rapidly growing area of research. It has in recent times been more recognized that an underactive bladder may develop as a direct result of neurological injury and disease but also as a late development from an initially overactive bladder. However, mechanisms underlying the pathobiology of an underactive bladder are incompletely understood, and new experimental models are needed to address the needs for this underserved patient population. Chang and Havton reviews recently developed experimental models for neurogenic underactive bladder studies. Research on bladder control in the setting of neurological diseases has shown significant growth in recent years, and this progress is also reflected in the several contributions to this special issue. However, many challenges remains for this research field and will require collaborative and multi-disciplinary approaches to overcome. Some of these challenges include the identification of the most promising basic science discoveries for clinical translation and the development and validation of pre-clinical models that are the most relevant for human neurological conditions. It is my hope that the research articles in this special issue will increase awareness in the research community about the importance of research on lower urinary tract dysfunction and stimulate both established and young investigators to continue the development of improved experimental models and approaches for the study of bladder function in the setting of neurological conditions. Leif A. Havton Departments of Neurology and Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 E-mail address: [email protected]